Nitrosourea induced nervous system tumors in rats will be used for the study of some biochemical properties which may differ significantly from normal brain and which may have application in experimental therapies. Studies on the differing responses of tumor lysosomes to labilization with X-radiation and Vitamin A will be extended to gliomas and neurinomas obtained at early periods after treatment and measured for total activities and latencies of beta-glucuronidase, N-acetyl- glucosaminidase, acid phosphatase, arylsulphatase and acid protease. A standardized fractionation procedure will be sought for the isolation of lysosomes and other subcellular particles from rat and human gliomas, based on sedimentation and density characteristics of the particles, and monitored by enzyme markers and electron microscopy. Ultramicrochemical assays of four acid hydrolases will be performed on microdissected gliomas for the evaluation of enzyme distributions in reference to growth zones. Cerebral tissues surrounding gliomas will be studied for possible alterations in hydrolase activities and latencies. Monolayer a cultures of cloned astrocytes will be studied for hydrolase activities and for the responses of hydrolases to attempted in vitro carcinogenesis with MNU. Cultures of glioblastoma will be studied for degree of activity upon extracellularly presented substrates of the acid hydrolases. The contribution of the pentose cycle in metabolism of gliomas will be assessed by the Hostetler Method using randomization of glucose-2-C14 in vivo and by measurement of intermediaries of the cycle in frozen tissues. Application of the Siesjo Method for intracellular pH determination will be attempted in the gliomas. Local blood flow will be measured using C14 antipyrine in growth zones of gliomas and in surrounding brain. If our preliminary results of decreased flow in surrounding brain are confirmed, the degree of autoregulation and response to steroids will be assessed.